反应详情

To a solution of 1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid (0.500 g, 1.94 mmol), 1-(3-bromophenyl)cyclopropanamine (453 mg, 2.14 mmol) and N,N-diisopropylethylamine (1.73 mL, 9.72 mmol) in DMF (18 mL) is added TBTU (0.780 g, 2.43 mmol). After 2 hours, the mixture is concentrated in vacuo, dissolved in ethyl acetate (200 mL), and washed with 2N sodium hydroxide (3×100 mL), saturated aqueous ammonium chloride (2×100 mL), saturated aqueous sodium bicarbonate (100 mL), brine (100 mL). The organic layer is dried over MgSO4, filtered through a pad of silica gel eluting with ethyl acetate (3×100 mL), and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with a gradient of 50-70% ethyl acetate in heptane to give a solid that is triturated with methylene chloride to afford the title compound as a solid.

1. concentrationthe mixture is concentrated in vacuo
2. dissolutiondissolved in ethyl acetate (200 mL)
3. washwashed with 2N sodium hydroxide (3×100 mL), saturated aqueous ammonium chloride (2×100 mL), saturated aqueous sodium bicarbonate (100 mL), brine (100 mL)
4. dry with materialThe organic layer is dried over MgSO4
5. filtrationfiltered through a pad of silica gel eluting with ethyl acetate (3×100 mL)
6. concentrationconcentrated in vacuo
7. customThe residue is purified by silica gel chromatography
8. washeluting with a gradient of 50-70% ethyl acetate in heptane
9. customto give a solid
10. customthat is triturated with methylene chloride